Cancer Cell:致癌突变的关键执行者

2014-04-17 佚名 生物通

科学家们发现,肠癌中的许多重要致癌基因都通过一种microRNA起作用,这一核心分子将成为相关药物开发的关键。文章于四月十四日发表在Cancer Cell杂志上。研究指出,靶标这种microRNA的药物可以同时阻断多个致癌突变的影响,此外这种分子的水平还可以帮助人们预测肠癌的侵袭性。格拉斯哥大学和俄亥俄州立大学的研究人员,检测了485名肠癌患者体内的microRNA 135b水平。他们发现,这种分

科学家们发现,肠癌中的许多重要致癌基因都通过一种microRNA起作用,这一核心分子将成为相关药物开发的关键。文章于四月十四日发表在Cancer Cell杂志上。研究指出,靶标这种microRNA的药物可以同时阻断多个致癌突变的影响,此外这种分子的水平还可以帮助人们预测肠癌的侵袭性。

格拉斯哥大学和俄亥俄州立大学的研究人员,检测了485名肠癌患者体内的microRNA 135b水平。他们发现,这种分子在肿瘤中的水平至少是健康组织的四倍,而且microRNA 135b水平最高的患者活得最短。

研究还显示,在小鼠肠癌模型中阻断microRNA 135b可以停止肿瘤生长。研究人员发现,约有半数的肿瘤大幅缩水,甚至无法通过成像技术观察到。到目前为止,这种治疗方案还没有显示出任何副作用。

MicroRNA能够通过调控基因活性,参与许多重要的细胞过程。研究人员指出,许多已知的癌基因突变(APC、PI3KCA、SRC和p53)都通过microRNA 135b起作用。尽管人们已经开发了一些靶标肠癌突变的药物,但患者常常会对它们产生抗性。抑制microRNA 135b能够同时阻断多个致癌突变的作用,有望成为不引起抗性的抗癌新途径。

研究人员还强调,检测患者的microRNA 135b水平,可以帮助医生发现可能出现侵袭性肠癌的患者,并及时对他们进行强化治疗。

文章的第一作者Dr Nicola Valeri介绍道,“我们向人们展示,特定microRNA是许多致癌突变的关键执行者,推动着肠癌的生长和发展。microRNA 135b水平最高的肠癌患者最难医治。研究显示,在小鼠中抑制该分子可以阻止肿瘤的生长。虽然这项研究还处于初级阶段,但我们相信这些发现将对肠癌患者的治疗方式产生重要影响。”

英国癌症研究所的Paul Workman教授评论道:“这一工作展现了microRNA在肠癌中的重要作用,开辟了癌症治疗的新途径,也为我们提供了宝贵的疾病指标,有助于在临床上预测患者的癌症发展。”

“细胞内的MicroRNA有着至关重要的作用。人们早已意识到microRNA对于癌症的重要性,但这类分子功能十分广泛,很难在靶标它们的同时避免毒副作用。不过microRNA 135b可能不存在这样的问题,因为它在正常组织中的水平非常低。”

文章作者之一,格拉斯哥大学的Owen Sansom教授说:“我们发现,一个简单的microRNA控制着肠癌中的多条通路。以此作为靶标进行治疗,将是肠癌患者的新希望。”

原始出处:

Valeri N1, Braconi C2, Gasparini P3, Murgia C4, Lampis A2, Paulus-Hock V2, Hart JR5, Ueno L5, Grivennikov SI6, Lovat F3, Paone A3, Cascione L3, Sumani KM3, Veronese A7, Fabbri M3, Carasi S3, Alder H3, Lanza G8, Gafa' R8, Moyer MP9, Ridgway RA4, Cordero J4, Nuovo GJ3, Frankel WL10, Rugge M11, Fassan M11, Groden J3, Vogt PK5, Karin M6, Sansom OJ4, Croce CM12.MicroRNA-135b Promotes Cancer Progression by Acting as a Downstream Effector of Oncogenic Pathways in Colon Cancer.Cancer Cell. 2014 Apr 14;25(4):469-83. doi: 10.1016/j.ccr.2014.03.006.

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    2015-01-29 维他命
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    2014-04-19 jambiya

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